Although lipid peroxidation products have been implicated in oxidative stress-related diseases, pretreatment of cells with such compounds at sublethal concentrations shows significant cytoprotective effects against forthcoming oxidative stress. The adaptive response induced by 4-hydroxynonenal (HNE) is critically mediated by gene expression of cytoprotective proteins via NF-E2-related factor 2/Kelch-like-ECH-associated protein 1 (Nrf2/Keap-1) pathway. The physical or mechanical stimuli such as shear stress also impose adaptive responses by inducing gene expression. Laminar shear stress, anti-atherogenic shear stress activates Nrf2/Keap-1 pathway. The transcriptome analysis using DNA microarray reveal high similarity in gene expression profiles of cells treated with HNE and laminar shear stress, providing insight into molecular mechanisms. These findings suggest a general hormetic effect of diverse stimuli in cell cultures and may lead to a reappraisal of the eventual role of reactive oxygen species and lipid peroxidation in organisms.
Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used in Japan as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation (DIC), shock, and pancreatitis. Recent in vitro studies have demonstrated that serine protease inhibitors may have anti-inflammatory properties beyond their inhibition of neutrophil elastase at the site of inflammation. However, the therapeutic effects of UTI in vivo remain unclear. In this review, we introduce the roles of UTI in the experimental systemic inflammatory response induced by both intraperitoneal and intratracheal administration of lipopolysaccharide using UTI deficient and wild-type mice. Our experiments suggest that UTI can protect against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly, through the inhibition of proinflammatory cytokine and chemokine expression. UTI may therefore present an attractive “rescue” therapeutic option for systemic inflammatory response syndromes such as DIC, acute lung injury, and multiple organ dysfunction.
Properties of mutant δ-aminolevulinate dehydratase (ALAD) found in patients with ALAD porphyria were studied by enzymological and immunological analyses after the synthesis of enzyme complexes using a cell-free system. Enzyme activities of homozygous G133R, K59N/G133R, V153M, and E89K mutants were 11%, 22%, 67%, and 75% of the wild-type ALAD, respectively, whereas that of K59N, a normal variant, was 112%. Enzyme activities of L273R, C132R and F12L were undetectable. Co-synthesis of F12L, L273R, G133R, K59N/G133R, or C132R mutants with the wild-type at various ratios showed that ALAD activity was proportionally decreased in the amount of the wild-type in the complex. In contrast, co-synthesis of V153M, K59N, and E89K with the wild-type did not influence enzyme activity of the wild-type. Surface charge changes in K59N, E89K, C132R and G133R predicted by mutations were also confirmed by native polyacrylamide gel electrophoresis. A compound E89K and C132R complex showed ALAD activity similar to that was found in erythrocytes of the patient. These findings indicate that cell-free synthesis of ALAD proteins reflects enzymatic activities found in patients, and suggest that, in addition to the direct effect of mutations on the catalytic activity, conformational effects play an important role in determining enzyme activity.
The aim of this study was to examine whether malondialdehyde (MDA) formation, a marker of oxidant stress, is altered in different stages of development of hyperlipidemia and whether it correlates with atherogenic index (AI), an important risk factor of atherosclerosis. Commercial kits were used to measure the levels of lipid profile and antioxidant status in the serum of 15 hyperlipidemic patients and 30 age and sex-matched normolipidemic subjects. The normolipidemic subjects were divided into lower and higher lipid groups according to their blood lipid level. The activities of superoxide dismutase and glutathione peroxidase decreased in higher lipid group compared with lower lipid group, and were even lower in hyperlipidemic subjects. An increase in the levels of MDA, triglycerides, total cholesterol and LDL-C concentration were observed in higher lipid group, and even significantly increased in hyperlipidemic patients. A significant progressive decline in HDL-C concentration was found during hyperlipidemia evolution. There was a positive correlation between MDA and AI (r = 0.61, p<0.05). These data indicate that oxidative stress is an early event in the evolution of hyperlipidemia, and appropriate support for enhancing antioxidant supply in higher lipid subjects may help prevent the course of the disease.
The effects of inulin on the microbial composition and faecal characteristics in 36 healthy, formula-fed infants (average age 7.7 months) given 3 different daily dosages of native inulin (0.75 g/day, 1.00 g/day, and 1.25 g/day) were studied. At all levels of inulin consumption, a significant (p<0.05) reduction of potential pathogenic microorganisms such as clostridia was found. An intake of 1.25 g/day of inulin caused a significant (p<0.05) increase of Bifidobacterium spp. as well as a significant (p<0.05) decline in Gram-positive cocci and coliform bacteria. Inulin consumption resulted in a significant (p<0.05) decrease in faecal pH value and changes in faecal weight, faecal texture and colour, indicating improvement in healthy bile production and bacterial fermentation. It is concluded that inulin consumption in formula-fed infants after weaning positively affected the microbial composition of faeces and faecal properties.
Using high sucrose-fed male Sprague-Dawley rats, a study was conducted to determine the effects of feeding Galactomannan (GAL), a soluble dietary fiber extracted from Canadian-grown fenugreek seeds, on blood lipid and glucose responses. Rats (n = 8, 175–200 g) were randomly assigned to one of three high sucrose diets containing 10% cellulose (control), 7.5% cellulose + 2.5% GAL, and 5% cellulose + 5% GAL, respectively for 4 weeks. After 3 weeks, an oral glucose tolerance test (OGTT) was performed on each rat. A week later blood samples were collected to determine the effect on blood lipids. A significant reduction in glycemic response was observed only in 5% GAL group at 120 min following OGTT, when compared with that of control and 2.5% GAL groups. The plasma level of insulin was also significantly reduced (p<0.001) in 5% GAL-fed rats but at all times during OGTT. These animals also showed a reduction in body weight gain (p<0.05) in parallel with less food intake (p<0.05). All GAL-fed (2.5% and 5.0%) rats had significantly reduced plasma levels of triglycerides and total cholesterol in association with a reduction in epididymal adipose weight. Overall, this study demonstrated that feeding GAL from Canadian-grown fenugreek seeds has the potential to alter glycemic and lipidemic status and reduce abdominal fat in normal rats.
Dried-bonito broth (DBB, katsuo-bushi dashi) is commonly used in Japanese cuisine, and is also used as a traditional remedy for recovery from fatigue and improvement of blood circulation. To clarify the effect of DBB on blood pressure, oxidative stress and emotional states, a randomized crossover human trial was performed. Twenty-seven elderly Japanese subjects ingested DBB or water for one month. Measurement of blood pressure and urinary 8-hydroxydeoxyguanosine (8-OHdG) and evaluation of emotional states were performed before and after the ingestion periods. The changes in systolic blood pressure (SBP) during DBB ingestion was significantly lower than that during water ingestion (p = 0.037). Urinary 8-OHdG significantly decreased during DBB ingestion (p = 0.0002). Evaluation of emotional states indicated that composure significantly improved during DBB ingestion (p = 0.034). These results suggest that the daily ingestion of DBB lower SBP, reduce urinary 8-OHdG and might improve emotional states in elderly subjects.
We have previously shown that extremely high level of guanidino compounds such as methylguanidine (MG), known as a neurotoxin and also a nephrotoxin, generate reactive oxygen species (ROS) using an electron spin resonance (ESR) technique with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In this in vitro study, the inhibitory effect of fermented papaya preparation (SAIDO-PS501:PS-501) on hydroxyl radical (·OH) generation from MG was examined using an ESR spectrometry, and it was found that PS-501 suppressed ·OH generation from MG in a dose-dependent manner. The ID50 value of PS-501 was 8 mg/ml. On the contrary, glucose itself did not suppress ·OH generation from MG up to100 mg/ml, whereas PS-501 almost completely suppressed ·OH generation from MG at a dose of 100 mg/ml. These results imply that PS-501 itself may have a beneficial effect of preventing ROS- and MG-related diseases.
To determine the effects of combined supplementation with chromium (Cr) and vitamins C and E on oxidative stress in type 2 diabetes, adult subjects with HbA1c >8.5%. Subjects (n = 30) in this randomized, double blind, placebo-control study were divided into three groups (placebo, Cr or Cr + C + E) on daily treatment. The Cr group received 1000 μg of Cr (as Cr yeast); the Cr + C + E group received Cr (1000 μg as Cr yeast) together with vitamins C (1000 mg) and E (800 IU); and, a control group received a placebo. Baseline plasma Cr levels were not significant differences comparing the supplementation and placebo groups. Thiobarbituric acid reactive substances (TBARS) and total antioxidative status (TAS) were also not significant different. Following the 6-month study period, the plasma TBARS levels, fasting glucose, HbA1c and insulin resistance were significantly decreased in the Cr and Cr + C + E groups, but not for the placebo group. Plasma TAS and glutathione peroxidase were significantly higher for Cr and Cr + C + E groups relative to the placebo group. These findings suggest that Cr supplementation alone and combined of Cr together with vitamins C and E was effective for minimization of oxidative stress and improvement of glucose metabolism in type 2 DM patients.
Although it has been accepted that pulmonary exposure to diesel exhaust particles (DEP), representative constituents in particulate matter of mass median aerodynamic diameter < or 2.5 μm (PM2.5), exacerbates murine allergic asthma, the in vivo effects of DEP on their cellular events in the context of allergen-specific Th response have never been examined. The aim of this study is to elucidate whether in vivo repetitive exposure to DEP combined with allergen (ovalbumin) facilitate allergen-specific Th response in the lung using a simple ex vivo assay system. As a result, repetitive pulmonary exposure to DEP in vivo, if combined with allergen, amplifies ex vivo allergen-specific Th2 response in the lung compared to that to allergen alone, characterized by high levels of interleukin (IL)-4 and IL-5. The result suggests that in asthmatic subjects, DEP promote Th2-prone milieu in the lung, which additively/synergistically augment asthma pathophysiology in vivo.
The aim of this study was to investigate the effect of dietary lemon polyphenols on high-fat diet-induced obesity in mice, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. Mice were divided into three groups and fed either a low fat diet (LF) or a high fat diet (HF) or a high fat diet supplemented with 0.5% w/w lemon polyphenols (LP) extracted from lemon peel for 12 weeks. Body weight gain, fat pad accumulation, the development of hyperlipidemia, hyperglycemia, and insulin resistance were significantly suppressed by lemon polyphenols. Supplementation with lemon polyphenols also significantly up-regulated the mRNA level of the peroxisome proliferator activated receptor-α (PPARα) compared to the LF and HF groups in the liver. Furthermore, the mRNA level of acyl-CoA oxidase (ACO) was up-regulated in the LP group compared to the LF group, but not HF group in the liver, and was also significantly increased in the epididymal white adipose tissue. Thus, feeding with lemon polyphenols suppressed body weight gain and body fat accumulation by increasing peroxisomal β-oxidation through up-regulation of the mRNA level of ACO in the liver and white adipose tissue, which was likely mediated via up-regulation of the mRNA levels of PPARα.
We compared three groups of pregnant women: placebo with normotensive women, group A which included preeclamptics, and group B which comprised preeclamptics who were supplemented their diets with vitamins C and E. MDA increased from 6.22 ± 2.8 (placebo) to 8.48 ± 1.2 (A) and 8.02 ± 1.8 nmol/gHb (B). NO concentrations were enhanced from 19.3 ± 4.2 (P) to 23.8 ± 6.4 (A) and 24.1 ± 5.4 μmol/L (B). GSH contents were decreased from 10.42 ± 2.81 (P) to 8.02 ± 2.92 (A) and 9.39 ± 1.02 μmol/g Hb (B), whereas GSSG concentrations increased from 0.98 ± 0.28 (P) to 1.24 ± 0.29 (A) and 1.08 ± 0.12 μmol/g Hb (B). SOD activity decreased 23% in A and 14% in B; GRx decreased 27% in A and 5.5% in B; GPx decreased 12% in A and 9.6% in B. Catalase activity, however, increased 27% in A and 29% in B as compared to control. Thus, we conclude that the use of vitamins C and E should be considered for the control of certain important biochemical indices during the development of preeclampsia; however, further studies are needed to develop methods for the prevention of preeclampsia in women at high risk.